Somatic rearrangement of T-cell antigen receptor gene in human T-cell malignancies.

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Abstract
A cDNA [complementary DNA] clone representing the gene encoding the .beta. chain of the human T-cell antigen receptor was used as hybridization probes in Southern blot analysis of restriction endonuclease-digested genomic DNA to examine the structure of the gene in DNA from 26 patients with acute leukemia and from 23 normal individuals. The T-cell antigen receptor gene had undergone somatic rearrangement in 14 of 14 patients with the phenotypic diagnosis of T-cell acute lymphoblastic leukemia. In this group of patients, similar patterns of rearrangement appear to have occurred in different patients. This finding suggests that there is either a limited repertoire of possible rearrangements or an association between the development of leukemia and specific patterns of rearrangement. DNA from 6 patients with acute myeloblastic leukemia, 6 patients with non-B, non-T acute lymphoblastic leukemia and 23 nonleukemic individuals showed no rearrangement or polymorphism. One case of T-cell acute lymphoblastic leukemia showed rearrangement of both the T-cell receptor .beta. chain and the constant region of the Ig gene. Studies with mixtures of DNA from leukemic bone marrow cells and cultured skin fibroblasts, as well as with remission and relapse marrow DNA from the same patients, indicate that this technique can detect 1% leukemia cells in a mixed population. DNA from the marrow of a patient in relapse contains a similar rearrangement to that found in the marrow sample taken at the time of diagnosis, which suggests that the original clone of leukemic cells was responsible for relapse. Assessment of rearrangement of the T-cell antigen receptor gene could be valuable in the diagnosis and management of leukemia and can be used to evaluate clonality in T-cell neoplasia.